Bioactive materials including drugs, hormones and the like are administered to animals by injection of liquid formulations or implantation of solid compositions. While injections may be made on a daily basis, sustained release formulations are usually preferred for parenteral administration of bioactive materials to moderate the release of the active agent, to reduce initial spiking of concentrations in the body, and to reduce the frequency with which the material must be administered. This is particularly true in the case of hormones which are preferably administered to animals at a relatively constant rate over a period of several weeks or months.
Somatotropin, a growth hormone which can be produced reliably and inexpensively in large quantities by recombinant DNA technology, is known to be effective in increasing milk production of dairy cattle and in improving meat production of beef cattle and swine. Somatotropin formulations having prolonged release characteristics have been prepared by dispersing somatotropin in a vegetable oil carrier for injection as described for example in EP 177,478. Aqueous formulations of somatotropin intended for administration over an extended period by means of an implanted osmotic pump delivery device are described in U.S. Pat. No. 4,855,141.
Solid pellets of somatotropin adapted for parenteral administration by implantation and having at least one uncoated release surface are described in U.S. Pat. No. 4,863,736, incorporated herein by reference. According to this patent, solid pellets of somatotropin produced by recombinant DNA technology and which are essentially free of binder or matrix polymers are formed by dry compression. The pellets may be partially coated with a barrier type polymer to substantially inhibit release of the somatotropin from the coated surfaces. Examples of suitable materials that can be used to provide the partial coating for the somatotropin pellet are disclosed to include shellac, bees wax, cellulose acetate butyrate, polylactic acid, ethyl cellulose, silicones, ethylene vinyl acetate co-polymer, hydroxy propyl cellulose, polycarbonate, polycaprolactone cellulose acetate, polymethyl methacrylate and other polymers known for use as barrier coatings.
As further disclosed in this U.S. patent, at least one surface of the pellet is left uncoated to provide a primary release surface for the somatotropin. In the case where the pellet is formed in a cylindrical shape, it is generally preferred to coat the cylindrical surface while leaving one or both ends of the cylinder uncoated. The rate of release of somatotropin from a pellet partially coated with a barrier type polymer increases with the surface area of the uncoated portion.
As further disclosed in this reference at column 9, lines 32-63, the coated pellets may additionally be provided with a "temporary protective covering" i.e., a light polymeric covering "to protect the article during storage and handling, and possibly to be of assistance in the administration of the article to the animal." Such temporary protective coverings are either removed prior to implantation of the pellet or are quickly removed from the pellet by surrounding tissue fluids after implantation. In either case, the temporary protective covering is disclosed to have little or no effect on somatotropin release rates, and is thereby distinguished from the "coating" utilized for the purpose of providing prolonged release delivery as described in the reference. Suitable materials useful as such temporary protective coverings which dissolve and/or melt after implantation are reported to include polyvinyl alcohol, sugars and polyethylene glycol such as PEG 8000.
It is an object of the present invention to provide a new delivery system for the parenteral administration of somatotropin and other biologically active materials to animals. It is a further object of this invention to provide a solid pellet of somatotropin or other biologically active material having sustained release delivery characteristics. It is a yet further object of this invention to provide a coating for solid pellets of somatotropin and other biologically active materials which may be uniformly applied to all surfaces of the pellet to impart sustained release properties upon implantation. It is a yet further object of this invention to provide a solid pellet of somatotropin or other biologically active material which is totally eveloped by a polymeric coating which imparts prolonged release characteristics to the pellet through parenteral administration. These and other objects of this invention will be apparent from the ensuing description and Examples.